Research Terms
Medicinal Chemistry Pharmaceutics
Industries
Background:
Opportunistic Infections (OIs) caused by pathogenic microorganisms such as
Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus are growing
medical concerns for immuno-compromised patients such as those with AIDS,
diabetes, organ transplant patients, patients on cancer chemotherapy, and several
others. The burden imposed by these infections is staggering, both in terms of
economic loss and human suffering. In sub-Saharan Africa for example, 15-30% of all
patients with AIDS develop cryptococcal disease and cryptococcal meningitis occurs
in 30% of these individuals. If not properly treated, these OIs are often fatal.
Statement of Problem:
1.3 million people in the US are living with HIV, with 20% unaware of their status. With
their immune systems compromised, up to 90% will experience an OI episode. The
medications available for treating OIs are limited because they were not important
prior to the AIDS epidemic. Unfortunately, even the limited numbers are further limited
by resistance development, drug interactions and toxicity. Amphotericin B, the gold
standard for OI treatment produces nephrotoxicity in patients on the drug.
Potential Solution:
Our invention comprises the discovery and in vivo validation of the efficacy of
natural product?derived agents with potent, less toxic and overall better therapeutic
profiles than Amphotericin B. For example, one of the discoveries decreased brain
C. neoformans infections 50% more than Amphotericin B in animal models of the
infection. Because they have different mechanisms of action, these compounds will
be complementary to those currently on the market and might be useful in
treatment?resistant cases especially. Another exciting aspect is that unlike the drugs
on the market, external application of the new compounds would have limited
capacity to cause systemic toxicity.
The Benefits:
? The new drugs are effective against a broad spectrum of opportunistic infections
? They will treat opportunistic infections without nephrotoxicity.
? These drugs should be complementary to the drugs currently available and thus
might be useful in treatment-resistant cases.
Commercialization Status:
Indoloquinolinium salts and their derivatives are currently in the pre-clinical
development stage. This research has been funded by the National Institutes of
Health, NIAID/NCRR. Validation of the observed activities in larger animal models is
planned along with additional pharmacokinetic studies. We seek venture capitalists
and partners or licensees with interest in small molecule drug development in the
Biotechnology and/or Pharmaceutical Industries.
New butyrophenones have been shown to treat psychosis in vivo but unlike the standard drug haloperidol, does not produce Parkinsonism-like movement disorders. On the other hand, these compounds are as potent as clozapine but do not interact with receptors associated with the induction of weight gain.
Background:
Psychosis and specifically schizophrenia, is a very debilitating illness that has devastated the lives of many and their families. In the US, 1.1% of the population or about 4.1 million have been diagnosed with schizophrenia. Out of this number, up to a third of patients are treatment-resistant (TRS) and do not benefit from the medications currently available. In addition, schizophrenia is associated with suicidal ideation and somewhere between 9-13% of patients eventually take their own lives. Even more troubling is the fact that 65 to 80 % of outpatients with chronic schizophrenia discontinue their antipsychotic medications, often because of a lack of efficacy or intolerable adverse effects. Thus, new medications are urgently needed to replace those in current use.
Statement of Problem:
Of the two types of drugs currently used in the treatment of schizophrenia, the typical antipsychotics are very effective in treating the positive symptoms such as hallucinations, but they also produce serious movement disorders that often result in patients discontinuing the medications. Although still used, they have now been largely replaced by the atypical antipsychotics such as olanzapine. While movement disorders are generally lower with atypical antipsychotics, they often induce weight gain, metabolic disorders and Type II diabetes. Thus, new antipsychotic medications must overcome not only movement disorders but must not induce weight gain.
Potential Solution:
Based on the knowledge of the receptors responsible for the serious side effects, we have designed and now obtained new compounds demonstrated in animal studies to be as effective as clozapine but without neither the movement disorders or the weight gain even when tested at 5 times the therapeutic dose. Indeed, in a head to head evaluation of the binding profiles of the new agents with atypical antipsychotic agents currently in the clinic, the therapeutic potentials were superior in several cases. These compounds can be obtained in just three steps.
The Benefits:
New drugs will treat schizophrenia without producing movement disorders.
Drugs do not demonstrate the potential to produce weight gain or Type II diabetes,
Drug administration is similar to that employed in connection with olanzapine.
Commercialization Status:
Haloperidol analogs are currently in the pre-clinical development stage, and R&D is currently funded by the National Institutes of Health, NIGMS/MBRS Program. Validation of the observed activities in larger animal models is planned along with additional pharmacokinetic studies. We seek venture capitalists and partners or licensees with small molecule interest developments in the Biotechnology and/or Pharmaceutical Industries for commercialization.
Key Features:
Potential replacements for current antipsychotics without the associated weight gain or movement disorders.
Technology:
Drug replacements for the treatment of psychosis
Commercialization Status:
Haloperidol analogs are currently in the pre-clinical development stage, and R&D is currently funded by the National Institutes of Health, NIGMS/MBRS Program. Validation of the observed activities in larger animal models is planned along with additional pharmacokinetic studies. We seek venture capitalists and partners or licensees with small molecule interest developments in the Biotechnology and/or Pharmaceutical Industries for commercialization.
New indoloquinolinium salts and their derivatives have been obtained and have been shown to demonstrate potent anti-infective actions against opportunistic pathogens associated with HIV AIDS, cancer chemotherapy, organ transplant and other immune compromised conditions and could serve as replacement therapies for amphotericin B without the associated toxicity.
Background:
Opportunistic Infections (OIs) caused by pathogenic microorganisms such as Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus are growing medical concerns for immuno-compromised patients such as those with AIDS, diabetes, organ transplant patients, patients on cancer chemotherapy, and several others. The burden imposed by these infections is staggering, both in terms of economic loss and human suffering. In sub-Saharan Africa for example, 15-30% of all patients with AIDS develop cryptococcal disease and cryptococcal meningitis occurs in 30% of these individuals. If not properly treated, these OIs are often fatal.
Statement of Problem:
1.3 million people in the US are living with HIV, with 20% unaware of their status. With their immune systems compromised, up to 90% will experience an OI episode. The medications available for treating OIs are limited because they were not important prior to the AIDS epidemic. Unfortunately, even the limited numbers are further limited by resistance development, drug interactions and toxicity. Amphotericin B, the gold standard for OI treatment produces nephrotoxicity in patients on the drug.
Potential Solution:
Our invention comprises the discovery and in vivo validation of the efficacy of natural product-derived agents with potent, less toxic and overall better therapeutic profiles than Amphotericin B. For example, one of the discoveries decreased brain C. neoformans infections 50% more than Amphotericin B in animal models of the infection. Because they have different mechanisms of action, these compounds will be complementary to those currently on the market and might be useful in treatment-resistant cases especially. Another exciting aspect is that unlike the drugs on the market, external application of the new compounds would have limited capacity to cause systemic toxicity.
The Benefits:
Commercialization Status:
Indoloquinolinium salts and their derivatives are currently in the pre-clinical development stage. This research has been funded by the National Institutes of Health, NIAID/NCRR. Validation of the observed activities in larger animal models is planned along with additional pharmacokinetic studies. We seek venture capitalists and partners or licensees with interest in small molecule drug development in the Biotechnology and/or Pharmaceutical Industries.
Key Features:
Potential replacements for current anti-opportunistic infection agents with minimal side-effects.
Technology:
Drug treatment of OIs
Stage of Development:
Pre-clinical studies involving animal studies
Status:
Seeking research support to escalate animal studies, establish metabolic stability & pharmacokinetic profiles
